Long-Term Effects of Hydroxyurea in Children With Sickle Cell Anemia (The BABY HUG Follow-up Study)

Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Follow-up Study

Sickle cell anemia (SCA) is an inherited blood disorder that can cause organ damage. The BABY HUG study is evaluating the use of the medication hydroxyurea at preventing organ damage in children with SCA. The purpose of this follow-up study is to evaluate the long-term effects of hydroxyurea in children who have participated in the BABY HUG study.

Study Overview

• Status: Completed
• Conditions: Anemia, Sickle Cell
• Intervention / Treatment: Drug: Hydroxyurea

Detailed Description

SCA is an inherited blood disorder in which the body makes sickle-shaped red blood cells that contain abnormal hemoglobin. The sickled cells block blood flow in the vessels that lead to limbs and organs. This can cause pain, serious infections, and organ damage. The BABY HUG study (NCT00006400) is examining whether the medication hydroxyurea can prevent organ damage, especially in the spleen and kidneys, in children with SCA. This study is a follow-up study to the BABY HUG study and will enroll children who have participated in the BABY HUG study. The purpose of this study is to examine the long-term effects of using hydroxyurea as a treatment for SCA, including both the risks and benefits. Study researchers will also investigate the optimal age to begin treatment with hydroxyurea in children with SCA.

This study will enroll children between 2 and 7 years old who participated in the BABY HUG study. Hydroxyurea will not be provided to participants as part of this study, but participants may receive the medication from their own doctors. Parents of participants can choose for their child to participate in this study in one of two ways-by enrolling in either a passive follow-up group or an active follow-up group. For participants in the passive follow-up group, study researchers will review participants' medical records every 6 months, in addition to reviewing brain ultrasound tests and computed tomography (CT) or magnetic resonance imaging (MRI) scans, if completed. Participants will have a blood and urine collection at baseline and Year 4 (or at the end of the study, whichever comes first). Participants in the active follow-up group will take part in the same study procedures as participants in the passive follow-up group. In addition, at Year 2, participants in this group will undergo an additional blood and urine collection, a scanning procedure to obtain images of the liver and spleen, a kidney test, neuropsychological testing, and an ultrasound imaging test to evaluate liver and spleen size.

• Study Type: Observational
• Enrollment (Actual): 163

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
    • Washington, District of Columbia, United States, 20060
      • Howard University College of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan/Wayne State University
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New York
    • Brooklyn, New York, United States, 11203
      • Downstate Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • Drexel University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children from the initial BABY HUG study who agree to participate in this follow-up study.

Description

Inclusion Criteria:

• All children who completed at least 18 months of follow-up visits in the initial BABY HUG study
• Children from the initial BABY HUG study who are on a chronic transfusion program or who are recipients of a bone marrow transplant

Exclusion Criteria:

• Any child who was not enrolled in the initial BABY HUG study for at least 18 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Active Follow-up; An active follow-up involved the performance of many of the laboratory tests and procedures done during BABY HUG clinical trials study. These included, but not limited to, serial laboratory parameters that were not part of routine clinical care such as Hgb F levels, pitted cell count, Howell-Jolly Body determination, a liver-spleen scan, diethylenetriaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) measurement, creatinine clearance, Cystatin C, urine concentrating ability, transcranial Doppler, and neuropsychological testing.	Drug: Hydroxyurea; Parents and child's doctor may plan to use or not to use hydroxyurea.
Passive Follow-up; A passive follow-up involved the abstraction of clinical data from the medical record. Results of physical examinations and laboratory tests performed as part of routine clinical care were recorded.	Drug: Hydroxyurea; Parents and child's doctor may plan to use or not to use hydroxyurea.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo	The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes. The change in splenic function (worse vs not-worse) was compared between the randomized treatment groups (hydroxyurea vs placebo). The change in splenic function from baseline to 48 months was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased.	48 Months from the date of randomization
Change in Qualitative Spleen Function From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit	The change in splenic function from the randomized control trial baseline measurement was one of the primary outcomes.The change in splenic function (worse vs not-worse) was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit. The change in splenic function from baseline to 48 months was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, decreased to normal, absent to absent, or absent to decreased.	48 Months from the date of randomization
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo	The change in the percentage of pitted cell from randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between the randomized treatment groups (hydroxyurea vs placebo).	48 Months from the date of randomization
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo	The change in the percentage of pitted cell from randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between the randomized treatment groups (hydroxyurea vs placebo).	72 Months from the date of randomization
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit	The change in the percentage of pitted cell from the randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.	48 Months from the date of randomization
Change in the Percentage of Pitted Cell From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit	The change in the percentage of pitted cell from the randomized control trial baseline measurement was one of the primary outcomes. The change in the percentage of pitted cell was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.	72 Months from the date of randomization
Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo	The change in Howell-Jolly Bodies from randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between the randomized treatment groups (hydroxyurea vs placebo).	48 Months from the date of randomization
Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children Randomized to Hydroxyurea vs Placebo	The change in Howell-Jolly Bodies from randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between the randomized treatment groups (hydroxyurea vs placebo).	72 Months from the date of randomization
Change in Howell-Jolly Bodies (HJB) From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit	The change in Howell-Jolly Bodies from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.	48 Months from the date of randomization
Change in Howell-Jolly Bodies From Randomized Control Trial Baseline Measurement - Compared Between Children on Hydroxyurea vs Off Hydroxyurea at Study Visit	The change in Howell-Jolly Bodies (HJB) from the randomized control trial baseline measurement was one of the primary outcomes. The change in Howell-Jolly Bodies was compared between children who were known to be on hydroxyurea vs. off hydroxyurea at the time of the visit.	72 Months from the date of randomization

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: April 27, 2009
• First Submitted That Met QC Criteria: April 27, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Hydroxyurea; Sickle Cell Anemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: 647; N01 HB07160 (NHLBI)